CN112962125A - Method for preparing 64Ni target and 64Cu nuclide and application thereof - Google Patents

Method for preparing 64Ni target and 64Cu nuclide and application thereof Download PDF

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CN112962125A
CN112962125A CN202110181527.9A CN202110181527A CN112962125A CN 112962125 A CN112962125 A CN 112962125A CN 202110181527 A CN202110181527 A CN 202110181527A CN 112962125 A CN112962125 A CN 112962125A
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hydrochloric acid
gold
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CN112962125B (en
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温凯
马承伟
段菲
李超
李光
陈孟毅
赵海龙
王春林
王晓明
褚浩淼
王成志
刘涉洋
李洪玉
邓雪松
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Atom High Tech Co ltd
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    • C25D5/00Electroplating characterised by the process; Pretreatment or after-treatment of workpieces
    • C25D5/10Electroplating with more than one layer of the same or of different metals
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    • A61K51/0482Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group chelates from cyclic ligands, e.g. DOTA
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    • C25D3/48Electroplating: Baths therefor from solutions of gold
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    • C25ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25DPROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D5/00Electroplating characterised by the process; Pretreatment or after-treatment of workpieces
    • C25D5/48After-treatment of electroplated surfaces

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Abstract

The invention provides a method for preparing a 64Ni target and a 64Cu nuclide and application thereof. The above-mentioned64The preparation method of the Ni target comprises the following steps: preparing a gold-plated target body; carrying out acid soaking treatment on the gold-plated target body, repeating the soaking process once, and soaking for the second time to obtain a leachate with the Cu content not higher than 0.250 mu g/mL; plating enrichment on the surface of a gold-plated target64A Ni layer. Book (I)The invention further prepares64Irradiating the Ni target to obtain Ni-containing alloy64A target of Cu; to the said container64Sequentially carrying out target dissolving, separation and purification on the target piece of Cu to obtain the target64Cu species. The method of the invention can stably produce64Cu species, and the64The metal impurities in the Cu nuclide are obviously reduced, the preparation requirement of the radiopharmaceuticals can be met, meanwhile, the product quality is controllable, the stability of different batches is high, and batch and large-scale production is realized.

Description

Method for preparing 64Ni target and 64Cu nuclide and application thereof
Technical Field
The invention relates to the technical field of radioactive nuclide, in particular to a method for preparing64A Ni target,64A method of Cu species and applications thereof.
Background
64Cu is an important medical radionuclide, has a half-life of 12.7h, and can emit beta+And beta-Electron, can be used for both PET imaging and radiotherapy. In recent years, with the rapid development of integrated diagnosis and treatment technology, the technology is related to64The research of Cu medicine is more and more related to scholars at home and abroadNote that the number of the holes is equal to or less than the number of the holes,64cu labeled drugs have been widely used in the diagnosis of neuroendocrine tumors, tumor hypoxic tissue, Alzheimer's disease, and the like. On a day of 09 months and 04 days in 2020,64Cu-DOTATATE is marketed by FDA for use in the diagnosis of neuroendocrine tumors. The field of nuclear medicine64Study and pair of Cu-labeled drugs64The demand for Cu species is also rapidly increasing, thus creating stable, mass production64The preparation process of the Cu nuclide is particularly important.
64The Cu nuclide has various preparation methods, and can be prepared by nuclear reaction through a reactor64Zn(n,p)64Cu, or may be obtained by an accelerator. By nuclear reaction using zinc as target material64Zn(d,2p)64Cu、66Zn(d,α)64Cu or68Zn(p,αn)64Cu, or nickel as target material through nuclear reaction64Ni(p,n)64Cu or64Ni(d,2n)64Cu is obtained. The method which is most widely applied at present is bombardment enrichment by a 12-18MeV proton cyclotron64Preparation of Ni target material64Cu nuclide prepared by the method64The Cu nuclide has limited productivity which is generally about 3.7GBq, and the impurity content is high, so that the specific activity is low, and the marking rate is low in the drug marking process.
Therefore, the mass production and the stable preparation64Methods for Cu species remain to be investigated.
Disclosure of Invention
In order to solve the above problems, the present invention provides a method for preparing64A Ni target,64A method of Cu species and applications thereof. The method of the invention can stably produce64Cu species, and the64The metal impurities in the Cu nuclide are obviously reduced, the preparation requirement of the radiopharmaceuticals can be met, meanwhile, the product quality is controllable, the stability of different batches is high, and batch and large-scale production is realized.
The technical scheme of the invention is as follows:
the invention provides, in a first aspect, a method64A method of making a Ni target, the method comprising: placing the copper substrate in a gold plating solution to perform a first electroplating processA gold plating layer is formed on the surface of the copper substrate to obtain a gold plating target body; placing the gold-plated target body in an acid solution for acid soaking treatment, repeating the soaking process once, and soaking for the second time to obtain a leachate with the Cu content not higher than 0.250 mu g/mL; placing the gold-plated target body subjected to the acid treatment in a nickel plating solution for secondary electroplating so as to form plating enrichment on the surface of the gold-plated layer64Ni layer, namely64A Ni target.
The purpose of arranging gold plating layer on the surface of copper target sheet is to prevent64The Ni target piece is copper-dissolved in the subsequent target dissolving step, thereby reducing64The content of metal impurities, especially Cu, in Cu nuclide to increase64Specific activity of Cu species. The inventors found that enrichment in electroplating64Before the step of Ni, even if the step of pre-plating a gold layer is adopted for the copper target sheet, the obtained64The Cu content in Cu nuclide still seriously exceeds the standard. The inventor further researches and discovers that the leaching amount of metal impurities in the subsequent target dissolving step can be reduced by carrying out specific acid soaking treatment on the gold-plated layer, and particularly when the Cu content in the leaching solution obtained by the second soaking is in a specific range, the prepared gold-plated layer is prepared64The Cu content in Cu nuclide is obviously reduced, and the Cu nuclide prepared by the method64The quality of Cu nuclide is stable and controllable.
Further, the acidic solution comprises hydrochloric acid and hydrogen peroxide, and the volume ratio of the hydrochloric acid to the hydrogen peroxide is 5: 2, the concentration of the hydrochloric acid is 4-8mol/L, the concentration of the hydrogen peroxide is 25-35%, the soaking temperature is 80-90 ℃, and the soaking time is 10-20 min.
Further, the surface gloss of the copper substrate is grade 1-2. Researches show that the defects of pockmarks, pores and the like of the gold-plated layer can be reduced by electroplating the gold-plated layer on the surface of the copper substrate with specific roughness, so that the defects of pockmarks, pores and the like of the gold-plated layer can be well reduced64Cu content in Cu nuclide.
Further, the thickness of the gold-plated layer is 30-50mg/cm2Said enrichment of64The thickness of the Ni layer is 7-17mg/cm2
Furthermore, the content of the chloroauric acid Cu adopted by the gold plating solution is less than 0.3 mu g/g.
Study ofIt is shown that the first and second images,64cu contained in the reagent used in the Ni target fabrication process is directly introduced into the final product to affect64Mass of Cu species. Chloroauric acid is used as a main reagent in the gold plating process, and when the Cu content in the selected chloroauric acid is less than 0.3 mu g/g, the chloroauric acid is favorable for controlling64The Cu content in Cu nuclide is further increased64Mass of Cu species.
Further, a vertical electroplating bath is adopted for carrying out first electroplating, the current of the first electroplating is 5-75mA, the time is 2-4h, and the stirring rotating speed is 500-.
Researches show that in the gold plating process, more hydrogen is separated out from the plating tank, and if a horizontal plating tank is adopted, the defects of pockmarks, pores and the like of the gold-plated layer are easily caused. The stirring device is convenient to mount in the vertical plating bath, so that the stirring speed of the plating solution can be increased, the bubble amount attached to the surface of the cathode can be reduced, the gold-plated layer is more smooth, and the defects of pockmarks, pores and the like of the gold-plated layer are reduced during electroplating, thereby better reducing the defects of the gold-plated layer64Cu content in Cu nuclide.
Further, the nickel plating solution comprises hydrochloric acid and64ni ions, the concentration of the hydrochloric acid is 0.05-0.15mol/L, and the hydrochloric acid is64The concentration of Ni ions is 40-60 mg/mL.
Further, the temperature of the second electroplating is 20-60 ℃, and the current density is 20-50mA/cm2The positive pulse width is 500-700 mu s, the negative pulse width is 20-50 mu s, the period is 1ms, and the plating time is 0.5-2 h.
Further, the method further comprises: after the step of performing the second electroplating, the nickel plating solution is subjected to: evaporating to dryness after the nickel plating solution completely decays, adding hydrochloric acid for redissolving, adsorbing by AG1-X8 anion resin column, desorbing, collecting desorption solution, evaporating to dryness again to obtain purified enriched solution64Ni。
Enrichment of64The price of Ni is high, and after the nickel electroplating process is finished, the completely decayed nickel plating solution is recycled and purified, so that the metal impurities accumulated in the nickel plating solution can be effectively reduced, and further, the repeated use of the nickel plating solution can not be influenced64The quality of Cu nuclide and the production cost can be reduced.
Another object of the present invention is to provide a process for preparing a polymer by the above process64A Ni target.
It is another object of the present invention to provide a method for producing64A method for producing a Cu species, the method comprising: for the foregoing64Irradiating the Ni target to obtain Ni-containing alloy64A target of Cu; to the said container64Sequentially carrying out target dissolving, separation and purification on the target piece of Cu to obtain the target64Cu species.
Further, a particle accelerator is adopted to correct the64Irradiating the Ni target; and/or the presence of a gas in the gas,
the particle accelerator is an 11-30MeV accelerator, and a Cyclone-30 accelerator is further preferred, wherein the proton beam energy of the Cyclone-30 accelerator is 14-16MeV, the beam intensity is 60-100 muA, and the irradiation time is 2-6 h.
Further, the target solution comprises: mixing the solution with64Placing a Cu target in an acid solution at 60-80 ℃, collecting a dissolving solution when no bubbles are precipitated on the surface of the target, and evaporating to dryness, wherein the acid solution comprises hydrochloric acid and hydrogen peroxide, and the volume ratio of the hydrochloric acid to the hydrogen peroxide is 2: 1, the concentration of hydrochloric acid is 4-8mol/L, and the concentration of hydrogen peroxide is 25-35%; and/or the presence of a gas in the gas,
the separation and purification comprises the following steps: after AG1-X8 anion exchange resin column is balanced, loading on the column, respectively eluting with 6mol/L hydrochloric acid, 4mol/L hydrochloric acid and 0.1mol/L hydrochloric acid to sequentially obtain enrichment64Metal impurities such as Ni, Fe and Co,64Cu species.
It is a further object of the present invention to provide a composition prepared by the method described above64Cu species.
It is a further object of the present invention to provide the above64Use of a Cu species for the preparation of a label, optionally for PET imaging. The research finds that the invention is adopted64The Cu nuclide is coupled with molecules containing ligands such as DOTA, NOTA and the like, so that rapid marking can be realized, the marking rate is higher than 95%, and the in vivo and in vitro stability is good.
Drawings
FIG. 1 shows an embodiment of the present invention1 provided with64A schematic structural diagram of the Ni target;
FIG. 2 is a scanning electron microscope result diagram of the gold-plated layer provided in example 4 of the present invention;
FIG. 3 is a diagram of the detection position and detection result of the spectrometer provided in embodiment 4 of the present invention;
FIG. 4 is a comparison of copper target wafers provided in example 4 of the present invention before and after polishing;
FIG. 5 shows a batch of lots provided in example 6 of the present invention64Gamma spectrum of radionuclide purity of Cu;
FIG. 6 shows a batch of lots provided in example 6 of the present invention64ITLC spectra of radiochemical purity of Cu nuclides;
FIG. 7 is a drawing provided in example 7 of the present invention64HPLC chromatogram of Cu-PSMA-617 labeling rate.
Detailed Description
The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention.
The examples, where specific techniques or conditions are not indicated, are to be construed according to the techniques or conditions described in the literature in the art or according to the product specifications. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products commercially available.
Reagent: hydrochloric acid, Tracemetal grade, Thermo Fisher, canada; AG1-X8 resin, 100-200 mesh, Bio-rad, USA; chloroauric acid, 99.9%, shanghai tsuo si chemical ltd; hydrogen peroxide, 30% by mass, analytically pure, chemical reagents of national drug group limited; absolute ethanol, analytically pure, chemical reagents of the national drug group, ltd; red copper target slice, non-standard processing; enrichment of64Ni, 99.52% abundance, Isoflex corporation, usa; ultrapure water, Millipore water purifier, usa; iTLC-SG paper, Agilent, USA.
The instrument comprises the following steps: ML303 electronic balance, Mettler Toledo, germany; 7800 inductively coupled plasma Mass Spectrometry (ICP-MS), Agilent, USA; AR2000 thin layer scanner, Eckert & Ziegler, germany; DSPEC 50 high purity germanium multichannel gamma spectrometer (HPGe), GMX30 detector, Ortec corporation, usa; a pulse power supply is made by self; overhead electric mixers, Changzhou Enpei Instrument manufacturing Ltd; CRC-55TW Activity Meter, Capintec, USA; 2470 fully automatic gamma counter, Perkin Elmer, USA; nova Nano SEM 450 field emission scanning electron microscope, FEI corp, usa; X-MaxN Large area SDD spectrometer, Oxford Instruments, UK.
Example 164Preparation of Ni target
1. Providing a copper substrate
The red copper target (size about 100 x 10mm) is mirror polished, the surface glossiness is 1-2 grade (brightness-mirror surface brightness), the surface is wiped to remove oil stains, and the target is cleaned, dried and weighed.
2. Preparation of gold-plated target body
Preparing a gold plating solution: dissolving chloroauric acid with a small amount of water, adding enough strong ammonia water while stirring to generate light red Au2O3·NH3Precipitating, filtering, washing the precipitate with water to be neutral. Mixing Au2O3·NH3Transferring the precipitate into KCN solution, heating to dissolve to obtain colorless transparent KAu (CN)4·H2And adding citric acid and strong ammonia water into the O solution, and filtering for later use.
Gold electroplating: and (5) adding water into the vertical electroplating bath for leak detection, and determining the assembly tightness. Loading into copper substrate, adding prepared gold plating solution, current 40mA, electroplating time 2-4h, stirring speed 900 r/min. And pouring out the plating solution after the electroplating is finished, and washing the electroplating bath by using a ferrous sulfate solution to remove the KCN remained in the bath. The gold-plated target body is removed, cleaned, dried and weighed. Because a highly toxic substance KCN is used in the gold plating process, the plating solution needs to be subjected to non-toxic treatment according to the amount of KCN used for preparing the gold plating solution and FeSO4Adding ferrous sulfate to KCN (0.5-0.6): 1mol ratio, adjusting pH to 4-6 with sulfuric acid or sodium hydroxide, and using KI and AgNO3Examination of CN-Whether the precipitation is complete.
3. Acid soaking treatment
The gold-plated target body and the target dissolving tank are cleaned by ultrapure water, and target loading and leakage testing are carried out. 10mL of 6mol/L hydrochloric acid and 4mL of 30% hydrogen peroxide were added, and the mixture was immersed in a water bath at 90 ℃ for 20min, and the acid immersion process was repeated once. Detection Using ICP-MSMeasuring Cu content in the leachate obtained by the second soaking, and when the Cu content in the leachate obtained by the second soaking is lower than 0.250 mu g/mL, the gold-plated target body can be used for electroplating enrichment64And (4) Ni process.
4. Enrichment by electroplating64Ni
Preparing a nickel plating solution: dissolving and enriching by using 15mL of 9mol/L hydrochloric acid64Ni, 1mL of 30% hydrogen peroxide was added, and the solution was evaporated to dryness after complete dissolution. 0.1mol/L hydrochloric acid is dissolved to prepare64Ni ion concentration is 50mg/mL, and a proper amount of ethanol is added as a depolarizer.
Enrichment by electroplating64Ni: uniformly electroplating on the gold plating layer of the gold-plated target body by a pulse electroplating method at 40 ℃ and a current density of 35mA/cm2The positive pulse width is 600 mu s, the negative pulse width is 40 mu s, the period is 1ms, and the electroplating time is 0.5-2 h.
The surface is smooth, flat, firm and compact64Ni target (see FIG. 1), obtained64The thickness of the gold-plating layer of the Ni target is 30-50mg/cm2Enrichment of64The thickness of the Ni coating is 7-17mg/cm2. The coating has no crack through thermal shock and falling tests.
Example 264Preparation of Cu nuclide
1. Irradiation of radiation
Prepared in example 164The Ni target is transferred to a Cyclone-30 accelerator for irradiation, the energy of proton beam is 14-16MeV, the beam intensity is 60-100 muA, and the irradiation time is 2-6h, thus obtaining the Ni target containing64A target of Cu species.
2. Dissolving target
After irradiation, the target is transferred to a hot chamber for separation. After checking the water bath tightness, 6mL of 6mol/L hydrochloric acid and 3mL of 30% hydrogen peroxide were added to the dissolution tank to dissolve the target under heating. Transferring the dissolving solution when no bubbles are separated out on the surface of the target; and (4) cleaning the dissolving tank by using ultrapure water, combining the solutions, heating and evaporating to obtain a solid, and unloading the target.
3. Separating and purifying
Taking pre-loaded AG1-X8 anion exchange resin column, washing with 6mol/L hydrochloric acid to ensure the balance of the ion exchange column. Dissolving the dried solid with 6mol/L hydrochloric acid, loading on the column, washing the material liquid bottle with 5mL of 6mol/L hydrochloric acid, and loading on the column. Respectively eluting with 6mol/L hydrochloric acid64Ni, 4mol/L hydrochloric acid elutes metal impurities such as Fe and Co, and 0.1mol/L hydrochloric acid elutes64Cu species. Obtained by separating an ion exchange column64Evaporating Cu nuclide to dryness, and re-dissolving with 0.1mol/L hydrochloric acid to obtain64Cu species product.
Comparative example 364Original preparation method of Cu nuclide
The differences of the method from the embodiment 2 include: using a red copper target sheet which is not subjected to polishing treatment as a copper substrate; common chloroauric acid (purchased from national medicine group, metal impurity is less than or equal to 0.2 percent) is used; electroplating gold by using a horizontal electroplating bath; electroplating enrichment of gold-plated target body64The acid soaking treatment is not carried out before Ni. Obtaining numbers 1-3 according to the described method64Cu species, the results are shown in Table 1.
TABLE 164Original preparation method result of Cu nuclide
Figure BDA0002941587150000081
Theoretically, nuclides produced by particle accelerators are unsupported, but due to the introduction of Cu impurities during production64The content of Cu in Cu nuclide seriously exceeds the standard, the specific activity is reduced, and the influence on the specific activity64Application in Cu-related medicaments. Prepared by the original method64The Cu content in the Cu nuclide reaches more than 2.97 mu g/GBq. And as the thickness of the gold-plated layer increases,64the Cu content in the Cu nuclide is not reduced correspondingly, which shows that64The excessive Cu content in the Cu nuclide is related to the quality of the gold plating layer, and the problems of excessive Cu content in the gold plating layer or the existence of pores and other defects of the gold plating layer can be solved.
Example 464Research on Cu nuclide preparation method
1. Acid soaking treatment
After the gold plating process is finished, the gold plating layer is subjected to acid soaking treatment to reduce the content of metal impurities in the gold plating layer so as to further improveHigh quality of gold plating layer. After the completion of gold plating, the target piece was fixed in a dissolution tank, 10mL of 6mol/L hydrochloric acid and 4mL of 30% hydrogen peroxide were added to the dissolution tank, and the mixture was immersed in a water bath at 90 ℃ for 20 minutes. And soaking each gold-plated target body twice by acid, taking a leaching solution, and measuring the impurity content by ICP-MS. The results of the test of the bonded gold plating layer (shown in Table 2) and64and (4) formulating the quality index of the target sheet according to the Cu nuclide detection result, namely, after the secondary acid treatment, the Cu content in the leaching solution is not higher than 0.250 mu g/mL.
TABLE 2 results of acid treatment of gold-plating layer
Figure BDA0002941587150000082
Figure BDA0002941587150000091
2. Gold plating layer
A gold layer was electroplated on the surface of a copper substrate, which was a red copper target without polishing, in accordance with the method described in example 1. Amplifying the gold-plated layer by 1500 times by using a scanning electron microscope, and analyzing the surface flatness of the gold-plated layer; and (4) combining the scanning result of the electron microscope, selecting an obvious defect part as a monitoring point, and performing energy spectrum analysis on the suspected pore by adopting an energy spectrum analysis method.
FIG. 2 shows the results of scanning electron microscopy of gold-plating layer, in which a represents target No. 1 (gold: 17.21 mg/m)2) And b represents target No. 2 (gold: 19.16mg/m2) And c represents a target piece No. 3 (gold: 10.55mg/m2) The result shows that after the amplification is 1500 times, the gold plating layers of the No. 1 to No. 3 target piece samples have defects, and the quality of the gold plating layers is not obviously improved along with the increase of the thickness of the gold plating layers.
And further researching whether the defects are pores or not, randomly selecting two suspected pores on the coating of the No. 1 target piece for further amplification and observation, and analyzing the element types of the suspected pore areas on the No. 1 target piece by using an energy spectrometer. FIG. 3 shows the position and result of the spectrometer, wherein a represents the point of the spectrometer; b represents a checkpoint 10 map; c represents energyDetecting points by a spectrometer; d represents the checkpoint 26 map. The results show that Cu element is detected at two sampling points, and Si element and O element are detected at two sampling points, and the content is high. The result shows that the surface of the gold plating layer has pores, and the gold plating layer may have solid particles such as sand and the like, which have great influence on the quality of the gold plating layer, so that Cu is dissolved out in the subsequent target dissolving step, and the Cu is dissolved out64The Cu content in the Cu nuclide is higher.
The scanning electron microscope result further shows that the quality of the gold plating layer is poor in the scratch area of the copper target, which indicates that the roughness of the copper substrate directly influences the quality of the gold plating layer. The current density at the microcosmic convex position of the scratch area is high, and Au is easier to deposit; and the gold plating layer is not easy to deposit in the concave position, which can cause uneven texture of the gold plating layer.
When the surface of the copper target sheet is rough, coating cracks and pits are easily caused, the copper target sheet is polished to achieve the mirror polishing effect, so that the surface brightness and the flatness of the copper target sheet are obviously improved (see figure 4), the gold-plated layer is favorably attached, and the quality of the gold-plated layer is also improved. Furthermore, the surface of the polished copper target sheet is degreased and decontaminated by using a surfactant, so that the influence of oil stains on the coating is reduced.
3. Chloroauric acid
In that64During the preparation of the Cu species, impurity elements in the used reagents are directly introduced into the final product. Therefore, the reagents used were selected as best as Trace metal grade, the water used was obtained from Millipore ultra pure water machine, and other reagents required control of Cu impurity content. The results of ICP-MS impurity analysis of common chloroauric acid and high quality chloroauric acid as the main reagents in the gold plating process are shown in Table 3.
TABLE 3 Cu content in chloroauric acid samples
Figure BDA0002941587150000101
As shown in Table 3, the Cu content in the high-quality chloroauric acid is less than 0.3 mug/g, which is much lower than 52.22 mug/g of the common chloroauric acid, so that the high-quality chloroauric acid can reduce the content of the gold-plated layerAnd further facilitates control of Cu content64Cu content in Cu species.
4. Electroplating bath
In the gold plating process, hydrogen is generated by electrolysis of the cathode due to the existence of electrolysis side reaction, and gas precipitated under the condition of no stirring is more easily adhered to the surface of the cathode in the form of bubbles, so that the defects of pits, pinholes and the like appear in the gold plating layer, the quality of the gold plating layer is poor, and the target body material is easily dissolved out. The vertical plating bath can be more conveniently provided with the stirring device, the stirring speed of the plating solution is increased, bubbles attached to the cathode in the target plating process are reduced, and the gold plating layer is more smooth.
The above results show that it is possible to obtain,64the excessive Cu impurity content in the Cu nuclide is mainly related to the quality of the gold plating layer. First, the gold plating layer has poor surface flatness and fine pores in the plating layer, which cannot isolate the copper target, resulting in dissolution of Cu in the target dissolution step. Secondly, if the content of impurities such as Cu in the chloroauric acid reagent used for gold plating is high, Cu is deposited on the target sheet together with gold atoms, thereby affecting the quality of the final product. Again, the process of the present invention,64too high Cu content in Cu nuclide and process conditions, such as the type of electroplating bath used and the enrichment of gold-plated target body in electroplating64Whether the acid soaking treatment is performed before Ni or not, so that the quality control of the target making process is required to obtain high quality64Cu species.
EXAMPLE 5 enrichment in recovered purified Nickel plating baths64Ni
Enrichment of64Factors such as recycling of Ni and metal shavings may also cause accumulation or introduction of impurities, and thus the recovered nickel plating solution needs to be subjected to a purification treatment.
Enrichment by electroplating64After the Ni process is finished, transferring the nickel plating solution, evaporating to dryness after the nickel plating solution is completely decayed, adding 6mol/L hydrochloric acid for redissolution, adding the mixture into an AG1-X8 anionic resin column pre-balanced by 6mol/L hydrochloric acid, adding 6mol/L hydrochloric acid for desorption, collecting desorption solution to obtain purified enriched and enriched solution64Ni。
Enrichment can be achieved by repeating the column procedure one to two times64Purification and enrichment of Ni64Evaporating Ni solution to dryness for later use. Recovering and enriching64The impurity contents before and after Ni purification are shown in table 4.
TABLE 4 recovery enrichment64Impurity content before and after Ni purification
Figure BDA0002941587150000111
The result shows that the impurity content of the nickel plating solution is seriously exceeded due to the accumulation of impurities before purification. After purification treatment, the impurity content in the nickel plating solution is obviously reduced.
Example 664Cu nuclide preparation result
Prepared according to the method of example 264Cu species, the results are shown in Table 5.
TABLE 564Cu nuclide preparation result
Figure BDA0002941587150000121
The results show that within 3-4.5h of irradiation, the single batch yield reaches 19-45GBq (EOB); the yield reaches 182-252 MBq/muA.h, and the yield is higher; the impurity content is obviously reduced, and the Cu impurity content is controlled below 0.5 mu g/GBq.
For multiple batches64The quality of the Cu nuclide is checked, the activity is measured by an activity meter, and the activity of multiple batches is 22.2-55.5 GBq; multiple batches as determined by HPGe64The purity of Cu radioactive nuclei is more than 99.9 percent, and the purity of Cu radioactive nuclei is higher than that of Cu radioactive nuclei in a certain batch64The gamma spectrum of the radionuclide purity of Cu nuclide is shown in figure 5; the radiochemical purity of ITLC is more than 95 percent for a certain batch64The ITLC spectrum of the radiochemical purity of the Cu nuclide is shown in figure 6; the content of impurities of Ni, Co, Fe, Cu, Zn and Au is lower than 0.5 mu g/GBq by ICP-MS; the pH range is 1-3, and the medium is 0.01mol/L hydrochloric acid solution.
The above results show that64The Cu nuclide can meet the preparation requirement of the radiopharmaceuticals, and simultaneously realizes the stability, the mass production and the controllable quality64A Cu nuclide preparation process.
Example 7
64The Cu nuclide is mainly chelated to the radiopharmaceutical through a chelating agent in the molecule64Cu2+The method of (1) is completed. Can be used for64Cu-DOTATATE、64Cu-PSMA-617、64Preparation of markers such as Cu-ATSM. Under a specific pH value, the chelate reaction with a precursor compound is carried out for 10-15min, so that the rapid marking can be realized,64the Cu-PSMA-617 labeling rate was greater than 95% (FIG. 7).
Although the invention has been described in detail hereinabove with respect to a general description and specific embodiments thereof, it will be apparent to those skilled in the art that modifications or improvements may be made thereto based on the invention. Accordingly, such modifications and improvements are intended to be within the scope of the invention as claimed.

Claims (10)

1. A kind of64A method of making a Ni target, comprising:
placing a copper substrate in a gold plating solution for first electroplating so as to form a gold plating layer on the surface of the copper substrate, and obtaining a gold plating target body;
placing the gold-plated target body in an acid solution for acid soaking treatment, repeating the soaking process once, and soaking for the second time to obtain a leachate with the Cu content not higher than 0.250 mu g/mL;
placing the gold-plated target body subjected to the acid treatment in a nickel plating solution for secondary electroplating so as to form plating enrichment on the surface of the gold-plated layer64Ni layer, namely64A Ni target.
2. The method of claim 164The preparation method of the Ni target is characterized in that the acidic solution comprises hydrochloric acid and hydrogen peroxide, and the volume ratio of the hydrochloric acid to the hydrogen peroxide is 5: 2, the concentration of hydrochloric acid is 4-8mol/L, the concentration of hydrogen peroxide is 25-35%, the soaking temperature is 80-90 ℃, and the soaking time is 10-20 min; and/or the presence of a gas in the gas,
the surface glossiness of the copper substrate is 1-2 grades; and/or
Thickness of the gold plating layerIs 30-50mg/cm2Said enrichment of64The thickness of the Ni layer is 7-17mg/cm2
3. The method of claim 164The preparation method of the Ni target is characterized in that the Cu content of chloroauric acid adopted by the gold plating solution is less than 0.3 mu g/g; and/or the presence of a gas in the gas,
adopting a vertical electroplating bath to carry out first electroplating, wherein the current of the first electroplating is 5-75mA, the time is 2-4h, and the stirring rotating speed is 500-; and/or the presence of a gas in the gas,
the nickel plating solution comprises hydrochloric acid and64ni ions, the concentration of the hydrochloric acid is 0.05-0.15mol/L, and the hydrochloric acid is64The concentration of Ni ions is 40-60 mg/mL; and/or the presence of a gas in the gas,
the temperature of the second electroplating is 20-60 ℃, and the current density is 20-50mA/cm2The positive pulse width is 500-700 mu s, the negative pulse width is 20-50 mu s, the period is 1ms, and the plating time is 0.5-2 h.
4. The method according to any one of claims 1 to 364A method of making a Ni target, the method further comprising: after the step of performing the second electroplating, the nickel plating solution is subjected to:
evaporating to dryness after the nickel plating solution completely decays, adding hydrochloric acid for redissolving, adsorbing by AG1-X8 anion resin column, desorbing, collecting desorption solution, evaporating to dryness again to obtain purified enriched solution64Ni。
5. Prepared by the process of any one of claims 1 to 464A Ni target.
6. A kind of64A preparation method of Cu nuclide is characterized by comprising the following steps:
as described in claim 564Irradiating the Ni target to obtain Ni-containing alloy64A target of Cu;
to the said container64Sequentially carrying out target dissolving, separation and purification on the target piece of Cu to obtain the target64Cu species.
7. The method of claim 664The preparation method of Cu nuclide is characterized by adopting a particle accelerator to carry out reaction on the Cu nuclide64Irradiating the Ni target; and/or the presence of a gas in the gas,
the particle accelerator is an 11-30MeV accelerator, and a Cyclone-30 accelerator is further preferred, wherein the proton beam energy of the Cyclone-30 accelerator is 14-16MeV, the beam intensity is 60-100 muA, and the irradiation time is 2-6 h.
8. The method of claim 6 or 764The preparation method of the Cu nuclide is characterized in that the soluble target comprises the following steps: mixing the solution with64Placing a Cu target in an acid solution at 60-80 ℃, collecting a dissolving solution when no bubbles are precipitated on the surface of the target, and evaporating to dryness, wherein the acid solution comprises hydrochloric acid and hydrogen peroxide, and the volume ratio of the hydrochloric acid to the hydrogen peroxide is 2: 1, the concentration of hydrochloric acid is 4-8mol/L, and the concentration of hydrogen peroxide is 25-35%; and/or the presence of a gas in the gas,
the separation and purification comprises the following steps: after AG1-X8 anion exchange resin column is balanced, loading on the column, respectively eluting with 6mol/L hydrochloric acid, 4mol/L hydrochloric acid and 0.1mol/L hydrochloric acid to sequentially obtain enrichment64Impurities of Ni, Fe and Co,64Cu species.
9. Prepared by the process of any one of claims 6 to 864Cu species.
10. The method of claim 964Use of a Cu species for the preparation of a label, optionally for PET imaging.
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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113413637A (en) * 2021-06-25 2021-09-21 原子高科股份有限公司 Automatic radionuclide separation system and method
CN113877421A (en) * 2021-08-20 2022-01-04 苏州爱索拓普智能科技有限公司 Medical isotope separation and purification process
CN115432730A (en) * 2022-11-09 2022-12-06 南京硼高生物科技有限公司 Carrier-free medical isotope Cu-64 purification method and automatic purification process
US11964948B2 (en) 2022-06-07 2024-04-23 Actinium Pharmaceuticals, Inc. Bifunctional chelators and conjugates

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6011825A (en) * 1995-08-09 2000-01-04 Washington University Production of 64 Cu and other radionuclides using a charged-particle accelerator
CN1658938A (en) * 2002-04-12 2005-08-24 Pg研究基金会公司 Multicolumn selectivity inversion generator for production of high purity actinium for use in therapeutic nuclear medicine
KR20100085727A (en) * 2009-01-21 2010-07-29 재단법인 한국원자력의학원 Method of separating cu-64 from the enriched ni-64 target in which cu-64 is produced, to prepare cu-64
CN110853792A (en) * 2019-11-11 2020-02-28 西安迈斯拓扑科技有限公司 Method and apparatus for producing medical isotopes based on high power electron accelerators

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6011825A (en) * 1995-08-09 2000-01-04 Washington University Production of 64 Cu and other radionuclides using a charged-particle accelerator
CN1658938A (en) * 2002-04-12 2005-08-24 Pg研究基金会公司 Multicolumn selectivity inversion generator for production of high purity actinium for use in therapeutic nuclear medicine
KR20100085727A (en) * 2009-01-21 2010-07-29 재단법인 한국원자력의학원 Method of separating cu-64 from the enriched ni-64 target in which cu-64 is produced, to prepare cu-64
CN110853792A (en) * 2019-11-11 2020-02-28 西安迈斯拓扑科技有限公司 Method and apparatus for producing medical isotopes based on high power electron accelerators

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113413637A (en) * 2021-06-25 2021-09-21 原子高科股份有限公司 Automatic radionuclide separation system and method
CN113877421A (en) * 2021-08-20 2022-01-04 苏州爱索拓普智能科技有限公司 Medical isotope separation and purification process
US11964948B2 (en) 2022-06-07 2024-04-23 Actinium Pharmaceuticals, Inc. Bifunctional chelators and conjugates
US11975081B2 (en) 2022-06-07 2024-05-07 Actinium Pharmaceuticals, Inc. Bifunctional chelators and conjugates
CN115432730A (en) * 2022-11-09 2022-12-06 南京硼高生物科技有限公司 Carrier-free medical isotope Cu-64 purification method and automatic purification process

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